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Biomedical subjects

A Eldor

Publications and source records attributed to A Eldor.

At least 199 records · Page 11Linked to original sources
PubMed1984

Growth characteristics of human first trimester decidual cells cultured in serum-free medium: production of prolactin, prostaglandins and fibronectin.

A procedure for the establishment of pure human first trimester decidual cells in primary cultures has been developed. The high rate of success in obtaining such cultures resulted from the elimination of fibroblasts by appropriate enzyme dissociation and filtration of the initial tissue sample, and subsequent maintenance of the cells in a serum-free medium supplemented with insulin, fibroblast growth factor (FGF), estradiol, progesterone, hydrocortisone, transferrin and sodium selenite. Under these culture conditions, we obtained pure and actively dividing decidual cells forming tightly packed and nonoverlapping epithelioid cell monolayers covering more than 75% of the culture area. The cultured decidual cells retained their in vivo capacity to produce prolactin and various prostaglandins (PGs), primarily PGE2. There was a marked reduction in hormone production after 20 days in culture. A massive network of fibrillar surface fibronectin was detected by indirect immunofluorescence staining of the cultured cells. The production of prolactin and PGs together with the secretion of fibronectin may play a role in the implantation and subsequent growth of the embryo. The described procedure of obtaining fibroblast-free decidual cell monolayers will promote studies on the hormonal regulation of this tissue at the time of early intrauterine life.

Cells, Cultured↗
PubMed1984

Interferon enhances prostacyclin production by cultured vascular endothelial cells.

The effects of interferon (IFN) on the arachidonate metabolism and physiological functions of cultured endothelial cells and blood platelets have been examined. Cultured bovine aortic endothelial cells were found to be sensitive to the antiviral and antiproliferative activities of human leukocyte (alpha) IFN and to increase their capacity to synthesize prostacyclin (PGI2) upon exposure to IFN. Several observations indicate that IFN stimulates PGI2 synthesis at the level of the enzymes phospholipase A2 and cyclooxygenase: (a) PGI2 production was dependent upon the supply of exogenous arachidonic acid or the liberation of endogenous cellular arachidonate by ionophore A23187, but was not observed when IFN-treated cells were exposed to the endoperoxide prostaglandin H2. (b) IFN had no effect on the spontaneous release of PGI2 into the culture medium during the incubation period (24-72 h). (c) The stimulatory effect of IFN on PGI2 production was inhibited by both glucocorticoids and indomethacin. The effect of IFN on platelet prostaglandin metabolism was also investigated. Incubation of platelet-rich plasma with IFN had no effect on platelet aggregation and thromboxane A2 production. The biological significance of the findings presented in this paper may be considered in view of the protective role of PGI2 in the vessel wall and the fact that infection with certain viruses induces endothelial damage both in man and experimental animal models.

Animals↗
PubMed1984

Degradation of sulfated proteoglycans in the subendothelial extracellular matrix by human platelet heparitinase.

Cultured vascular and corneal endothelial cells produce an underlying extracellular matrix (ECM) which induces platelet adherence, aggregation, and release reaction. Incubation of a metabolically (35S)O = 4-labeled ECM with platelet-rich plasma or washed platelets, but not with platelet-poor plasma, resulted in degradation of its heparan sulfate-containing proteoglycans into labeled fragments four to five times smaller than intact glycosaminoglycan side chains. These fragments were sensitive to deamination with nitrous acid and were not produced in the presence of heparin, indicating that heparan sulfate in the ECM is susceptible to cleavage by the platelet heparitinase. This degradation required adhesion of platelets to the ECM rather than aggregation since it was not inhibited by aspirin, which prevented platelet aggregation but not adherence. The enzyme was not released during aggregation of platelets on the ECM but was readily liberated upon their exposure to thrombin. This liberation was inhibited in the presence of prostacyclin (PGI2). Isolated high molecular weight proteoglycans first released from the ECM by incubation with platelet poor plasma served as a substrate for further degradation by the platelet heparitinase, suggesting a cascade mechanism for degradation of heparan sulfate in the ECM. Heparitinase, although to a lower level, was also active when washed platelets were added on top of a confluent endothelial cell monolayer covering the (35S)O = 4-labeled ECM. It is suggested that the platelet heparitinase may be involved in the impairment of the integrity of the vessel wall and thus facilitate the extravasation of blood-borne cells.

Blood Platelets↗
PubMed1984

Thromboembolism in patients with the 'lupus'-type circulating anticoagulant.

Thirty-five patients with the lupus anticoagulant (LA) were followed up between 1975 and 1982. The most prevalent clinical manifestation occurring in these patients was thrombosis. Nineteen patients (54.3%) had a single or recurrent thrombotic episode. Fifteen patients (42.8%) had venous thrombosis, and arterial thrombosis manifested by stroke or transient ischemic attacks occurred in six patients. Bleeding occurred in only five patients, four of whom had severe thrombocytopenia, while no excessive bleeding was noted during 18 operative procedures. Various therapeutic regimens, including corticosteriods, nonsteroidal anti-inflammatory drugs, cytotoxic or immunosuppressive agents, had no effect on the presence of the LA in these patients. Anticoagulants were successful in the treatment and prevention of thrombotic episodes.

Adolescent↗
PubMed1983

Structural properties of myosin from the particulate fraction of human blood platelets.

Fractionation of human blood platelets has revealed that myosin, a contractile and mechanochemical protein, is present in both the soluble and particulate fraction. The aim of this study was to elucidate whether platelets contain more than one myosin isoform, especially in view of the fact that in other cellular systems (cardiac muscle, amoeba) several myosin isoenzymes were found. The particulate fraction was solubilized by Triton X-100, and the myosin was purified by the same procedure used for the cytoplasmic myosin. The final preparation contained, in addition to myosin, a 130-kDa polypeptide, which was observed also in myosin preparations obtained from the soluble fraction. The electrophoretic mobilities of the two myosins were identical under both dissociating and nondissociating conditions. Comparison of the molecular structure of the heavy chain of the two myosins by limited proteolysis with Staphylococcus aureus V8 protease showed that the proteolytic fragments of the two myosins were rather similar, with only minor alterations in the quantitative distribution of the products. Two-dimensional peptide mapping of the iodinated tryptic peptides of the myosin heavy chains indicated that at least one peptide is missing in the map of the particulate myosin, as compared to its soluble counterpart. According to the two-dimensional peptide map, the 130-kDa polypeptide seems to be a proteolytic fragment of the myosin heavy chain and most probably the rod portion of the molecule. The observed minor variations in the structure of myosins isolated from the soluble and the fractions of human platelets may reflect differences in their respective physiological functions.

Actomyosin↗
PubMed1983

Distribution of actin, myosin and actin binding protein in platelets of patients with hyperlipoproteinemia.

Significant anomalies in the quantity and relative distribution of the contractile proteins actin, myosin and actin binding protein (ABP) were observed in platelets obtained from patients with hyperbetalipoproteinemia (type IIa) and in patients with hypertriglyceridemia (type IV). Changes were observed in unfractionated platelets, (increased ABP in type IIa patients and increased actin in both type IIa and type IV) in isolated platelet membranes (increased ABP and actin in type IV, and increased myosin in type IIa) and in the KCl extract of platelets (increased actin in type IV and increased myosin in type IIa). The myosin ATPase specific activity was increased in platelets of type IV patients. No changes were observed in the concentrations and distribution of membrane glycoproteins in the platelets of these patients. The above anomalies in the contractile proteins might be relevant to the known functional anomalies of the platelets of patients with hyperlipoproteinemias.

Actins↗
PubMed1983

Platelet abnormalities in muscular dystrophy.

Platelets which have complex membranes and calcium shifts similar to those in muscles were investigated in 14 patients with muscular dystrophy and 20 suitable controls. In 4 Duchenne and one limb-girdle dystrophy aggregations were done and found to be depressed with adrenaline and ADP. Electron microscopic and chemical examinations revealed an increased number of dense bodies, changed permeability and/or binding of cations and elevated intracellular calcium in all the 9 cases of Duchenne dystrophy while the 2 limb-girdle and 3 myotonic dystrophies varied. A two phase polymer separation system applied to fixed platelets of all patients and controls showed no abnormality of surface negative charge.

Adolescent↗
PubMed1983

Effects of dipyrone on prostaglandin production by human platelets and cultured bovine aortic endothelial cells.

Dipyrone and its metabolites 4-methylaminoantipyrine, 4-aminoantipyrine, 4-acetylaminoantipyrine and 4-formylaminoantipyrine inhibited the formation of thromboxane A2 (TXA2) during in vitro platelet aggregation induced by ADP, epinephrine, collagen, ionophore A23187 and arachidonic acid. Inhibition occurred after a short incubation (30--40 sec) and depended on the concentration of the drug or its metabolites and the aggregating agents. The minimal inhibitory concentration of dipyrone needed to completely block aggregation varied between individual donors, and related directly to the inherent capacity of their platelets to synthesize TXA2. Incubation of dipyrone with cultured bovine aortic endothelial cells resulted in a time and dose dependent inhibition of the release of prostacyclin (PGI2) into the culture medium. However, inhibition was abolished when the drug was removed from the culture, or when the cells were stimulated to produce PGI2 with either arachidonic acid or ionophore A23187. These results indicate that dipyrone exerts its inhibitory effect on prostaglandins synthesis by platelets or endothelial cells through a competitive inhibition of the cyclooxygenase system.

Aminopyrine↗
PubMed1983

Bile salts facilitate the absorption of heparin from the intestine.

Heparin was absorbed through the rectal mucosa of rodents and primates only when administered in solutions containing sodium cholate or sodium deoxycholate (DOC). The absorption of heparin was monitored by following the increase in plasma radioactivity after administration of [35S]heparin, and by measurement of its biological effects: plasma lipase activity and prolongation of partial thromboplastin time (PTT). Following administration of the same concn of heparin in solutions lacking bile salts, there was almost no radioactivity in the blood, no prolongation of PTT and no release of plasma lipase activity. The PTT effect was found to be a less sensitive test of heparin absorption than the plasma lipase activity.

Animals↗
PubMed1983

Cultured endothelial cells increase their capacity to synthesize prostacyclin following the formation of a contact inhibited cell monolayer.

The synthesis of the prostaglandins (PG), prostacyclin (PGI2), PGE2, and thromboxane A2 (TXA2), has been investigated in actively growing and contact-inhibited bovine aortic endothelial cell cultures. Cells were stimulated to synthesize prostaglandins by exposure to exogenous arachidonic acid or to the endoperoxide PGH2 and by the liberation of endogenous arachidonic acid from cellular lipids with melittin or ionophore A23187. Increased capacity of the cells to synthesize PGI2 and PGE2 was observed as a function of time in culture, regardless of the type of stimulation. TXA2 production increased with time only upon stimulation of the cells with ionophore A23187. This increased PG synthetic capacity was independent of cell density since it was mainly observed in confluent, nondividing endothelial cell cultures. The fact that increased PGI2 production in confluent cells was also observed with PGH2, a direct stimulator of PGI2 synthetase, implies that this process is independent of the arachidonate concentration within the cells or in the culture medium. This increased capacity is likely to reflect an increased activity of the PG synthetase system associated with the formation of a contact inhibited endothelial cell monolayer. A similar time-dependent increase in the PGI2 production capacity was also observed during growth of cultured bovine corneal endothelial cells.

Animals↗
PubMed1983

The effect of radiation on prostacyclin (PGI2) production by cultured endothelial cells.

The effect of ionizing irradiation on the synthesis of prostacyclin (PGI2) by cultured bovine aortic endothelial cells was determined. PGI2 was measured in the culture medium by a radioimmunoassay for 6-Keto PGF1 alpha. Two phenomena were observed following irradiation: a) Cells which suffered an immediate radiation damage (1000-5000 rads) released high quantities of PGI2 to the culture medium. This was due to a de novo synthesis of PGI2 stimulated by radiation induced cellular damage, since pretreatment with aspirin of the endothelial cell monolayers resulted in a marked inhibition of PGI2 release following irradiation. b) Metabolically active cells which remained confluent and firmly attached to the culture dish following single, low and intermediate doses (200-1200 rads) radiation, exhibited a marked decrease in their capacity to synthesize PGI2 upon exposure to various stimuli of the arachidonic acid cascade (arachidonic acid, melittin, ionophore A23187 and PGH2). Similar results were observed with cells treated with fractionated radiation. The quantities of PGI2 produced by the endothelial cells decreased as a function of the dose of radiation and time interval between irradiation and subsequent stimulation. Radiation had a minimal effect on the nonthrombogenic properties of the endothelial cells, as evidenced by the small increase in platelet adherence to the endothelial cells. The effect of radiation on PGI2 production by the vascular endothelium may be relevant to the development of radiation induced capillary occlusions, and the enhancement of atherosclerotic lesions in large vessels.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Abnormalities of aggregation, thromboxane A2 synthesis, and 14C serotonin release in platelets of patients with idiopathic scoliosis.

Platelet functions were investigated in 16 patients with idiopathic scoliosis (IS), in seven patients with congenital scoliosis (CS), and in 12 healthy individuals who served as a control group. All were females, aged 11 to 22 years. Platelet aggregation anomalies were observed in all IS patients. These constituted an impaired platelet-release reaction when aggregation was induced with ADP or epinephrine, but not with collagen or arachidonic acid. A decreased thromboxane A2 synthesis and impaired 14C-serotonin release were also observed when platelets were stimulated with ADP or epinephrine. Platelet from CS patients and the controls did not show any functional abnormalities when stimulated with the above four aggregating agents. The platelet function anomaly in IS patients was not associated with prolongation of the bleeding time, spontaneous occurrence of hemorrhagic episodes, or increased bleeding during invasive procedures, including major spinal surgery. The above findings and the recently described platelet structural anomalies in IS may imply that the pathological process operative in idiopathic scoliosis involves not only the axial skeleton, but also cellular blood elements. The similarity between blood platelets and muscle cells, and the anomalies that have been found in both systems in IS, support the notion that a muscle disorder may be involved in the pathogenesis of the disease.

Adenosine Diphosphate↗
PubMed1983

The effect of long-term colchicine therapy in patients with recurrent polyserositis on the capacity of blood platelets to synthesize thromboxane A2.

Thromboxane B2 (TXB) production during platelet activation was measured in 13 patients with recurrent polyserositis on long-term colchicine therapy and 10 healthy controls. Plasma colchicine concentration in patients ranged between 0.8-7.8 ng/ml (2.0-19.5 X 10(-9) M). Thromboxane production induced during aggregation by arachidonic acid or collagen and serum TXB2 levels (clotted blood, 37 degrees C, 1 h) did not differ among patients and controls. Previous studies reporting platelet function defects including anomalous TXB2 production, were performed in vitro using colchicine concentrations markedly exceeding the therapeutic range.

Adolescent↗
PubMed1983

Acute surgical abdomen caused by thrombocytopenia in patients with acute leukemia and multiple myeloma.

One patient with multiple myeloma and four patients with acute leukemia presented with severe abdominal pain. Pertinent findings included numerous petechiae in the skin and buccal cavity, and diffuse abdominal guarding and tenderness, suggesting peritoneal involvement. Severe thrombocytopenia was found in all patients. Laparotomy was performed in the patient with multiple myeloma, and revealed numerous petechiae throughout the peritoneum. All five patients responded to platelet transfusions with disappearance of the abdominal signs and symptoms. Severe thrombocytopenia should be considered among the causes of acute surgical abdomen in patients with malignant hematological disorders, and platelet transfusions should be administered before any surgical intervention.

Abdomen, Acute↗
PubMed1982

Platelet interaction with the extracellular matrix produced by cultured endothelial cells: a model to study the thrombogenicity of isolated subendothelial basal lamina.

Cultured bovine endothelial cells produce an extensive underlying extracellular matrix (ECM) which closely resemble the vascular subendothelial basal lamina in its organization and chemical composition. This naturally produced ECM was used to study the interaction of platelets with the subendothelium when exposed or covered with vascular endothelial cells. Incubation of platelet rich plasma with the ECM induced a rapid and massive platelet adherence, aggregation, thromboxane formation and release reaction. These were demonstrated using phase and scanning electron microscopy, Indium-111 or (14C)-serotonin labelled platelets, and a radioimmunoassay for thromboxane B2. In contrast to the ECM no platelet activation was induced either by uncoated plastic dishes or ECM covered with a confluent endothelial cell monolayer. Aspirinized platelets failed to undergo aggregation and degranulation, when incubated with the ECM. Culture dishes coated with characteristic constituents of the basal lamina such as collagen type IV and type V or fibronectin induced a much lower platelet reactivity as compared with ECM coated dishes. Digestion of ECM components (collagen, fibronectin, hyaluronic acid, and chondroitin sulphate) by specific enzymes was not associated with a substantial decrease in its platelet reactivity. Furthermore, exposure of ECM to sodium dodecyl sulphate or sodium periodate, or freezing and thawing did not decrease its biological activity. In contrast, platelet activation was completely abolished following heat denaturation or glutaraldehyde fixation of the ECM. The availability of a naturally produced ECM provides an appropriate model to study the interaction of platelets with the subendothelium in a controlled system which is isolated from other components of the vessel wall.

Animals↗
PubMed1982

Prediction of haemorrhagic diathesis in thrombocytopenia by mean platelet volume.

The Coulter counter, model S Plus, Provides a platelet count and a mean platelet volume in all routine specimens of blood for cell count. The value of mean platelet volume in the prediction of the haemostatic potential of thrombocytopenic patients was investigated in 175 patients with haematological disorders who underwent 1473 blood counts over five months. Eighty-four haemorrhagic episodes were detected, most in thrombocytopenic patients. The mean platelet volume of patients with haemorrhagic tendency was significantly lower (5.52 +/- SD 0.7 fl) than that of patients without these tendencies (7.87 +/- SD 1.75 fl) (p less than 0.001). In cases of severe thrombocytopenia (less than 20 x 10(9)/1 platelets) haemorrhagic episodes were frequent; however, the frequency of bleeding was considerably lower in cases in which the mean platelet volume was higher than a suggested cut-off point of 6.4 fl. Discriminant analysis selected mean platelet volume as more important than platelet count for prediction of haemorrhagic state in severe thrombocytopenia. In view of the useful discrimination that mean platelet volume provides between thrombocytopenic patients who bleed and those who do not bleed, it may serve as a guide to predict the danger of haemorrhage and the need for prophylactic platelet transfusion.

Adolescent↗